tbuckley/cabot-search huggingface dataset:
Integrating physicomechanical and biological strategies for BTE: biomaterials-induced osteogenic differentiation of MSCs
Authors: Huixin Shi, Kaixuan Zhou, Mingfeng Wang, Ning Wang, Yiping Song, Wei Xiong, Shu Guo, Zhe Yi, Qiang Wang, Shude Yang
Journal: Theranostics (2023)

Large bone defects are a major global health concern.Bone tissue engineering (BTE) is the most promising alternative to avoid the drawbacks of autograft and allograft bone.Nevertheless, how to precisely control stem cell osteogenic differentiation has been a long-standing puzzle.Compared with biochemical cues, physicomechanical stimuli have been widely studied for their biosafety and stability.The mechanical properties of various biomaterials (polymers, bioceramics, metal and alloys) become the main source of physicomechanical stimuli.By altering the stiffness, viscoelasticity, and topography of materials, mechanical stimuli with different strengths transmit into precise signals that mediate osteogenic differentiation.In addition, externally mechanical forces also play a critical role in promoting osteogenesis, such as compression stress, tensile stress, fluid shear stress and vibration, etc.When exposed to mechanical forces, mesenchymal stem cells (MSCs) differentiate into osteogenic lineages by sensing mechanical stimuli through mechanical sensors, including integrin and focal adhesions (FAs), cytoskeleton, primary cilium, ions channels, gap junction, and activating osteogenic-related mechanotransduction pathways, such as yes associated proteins (YAP)/TAZ, MAPK, Rho-GTPases, Wnt/β-catenin, TGFβ superfamily, Notch signaling.This review summarizes various biomaterials that transmit mechanical signals, physicomechanical stimuli that directly regulate MSCs differentiation, and the mechanical transduction mechanisms of MSCs.This review provides a deep and broad understanding of mechanical transduction mechanisms and discusses the challenges that remained in clinical translocation as well as the outlook for the future improvements.
Integration of metabolomics and peptidomics reveals distinct molecular landscape of human diabetic kidney disease
Authors: Xinrong Jiang, Xingyue Liu, Xuetong Qu, Pingya Zhu, Fangjie Wo, Xinran Xu, Juan Jin, Qiang He, Jianmin Wu
Journal: Theranostics (2023)

Diabetic kidney disease (DKD) is the most common microvascular complication of diabetes, and there is an urgent need to discover reliable biomarkers for early diagnosis.Here, we established an effective urine multi-omics platform and integrated metabolomics and peptidomics to investigate the biological changes during DKD pathogenesis.Methods: Totally 766 volunteers (221 HC, 198 T2DM, 175 early DKD, 125 overt DKD, and 47 grey-zone T2DM patients with abnormal urinary mALB concentration) were included in this study.Non-targeted metabolic fingerprints of urine samples were acquired on matrix-free LDI-MS platform by the tip-contact extraction method using fluorinated ethylene propylene coated silicon nanowires chips (FEP@SiNWs), while peptide profiles hidden in urine samples were uncovered by MALDI-TOF MS after capturing urine peptides by porous silicon microparticles.Results: After multivariate analysis, ten metabolites and six peptides were verified to be stepwise regulated in different DKD stages.The altered metabolic pathways and biological processes associated with the DKD pathogenesis were concentrated in amino acid metabolism and cellular protein metabolic process, which were supported by renal transcriptomics.Interestingly, multi-omics significantly increased the diagnostic accuracy for both early DKD diagnosis and DKD status discrimination.Combined with machine learning, a stepwise prediction model was constructed and 89.9% of HC, 75.5% of T2DM, 69.6% of early DKD and 75.7% of overt DKD subjects in the external validation cohort were correctly classified.In addition, 87.5% of grey-zone patients were successfully distinguished from T2DM patients.Conclusion: This multi-omics platform displayed a satisfactory ability to explore molecular information and provided a new insight for establishing effective DKD management.
SPI1-mediated MIR222HG transcription promotes proneural-to-mesenchymal transition of glioma stem cells and immunosuppressive polarization of macrophages
Authors: Yang Fan, Zijie Gao, Jianye Xu, Huizhi Wang, Qindong Guo, Boyan Li, Ming Li, Hao Xu, Yanhua Qi, Shulin Zhao, Wei Qiu, Ziwen Pan, Qingtong Wang, Hao Xue, Rongrong Zhao, Xing Guo, Gang Li
Journal: Theranostics (2023)

Background: Glioma stem cells (GSCs) are a key factor in glioblastoma (GBM) development and treatment resistance.GSCs can be divided into the mesenchymal (MES) and proneural (PN) subtypes, and these two subtypes of GSCs can undergo interconversion under certain conditions.MES GSCs have higher malignancy and radioresistance and are closely associated with an immunosuppressive microenvironment.Long noncoding RNAs (lncRNAs) play a broad role in GBM, while the role of GSCs subtype remains unknown.Methods: We performed RNA sequencing to explore the lncRNA expression profile in MES-and PN-subtype GBM tissues.The biological function of a host gene-MIR222HG-in GBM development was confirmed in vitro and in vivo.Specifically, RNA sequencing, RNA pulldown, mass spectrometry, RIP, ChIP, luciferase reporter assays and Co-IP were performed.Results: MIR222HG, the expression of which can be induced by SPI1, has high levels in MES GBM tissues.Functionally, we demonstrated that MIR222HG promotes the MES transition and radioresistance in GSCs in vivo and in vitro.Mechanistically, MIR222HG can bind to the YWHAE/HDAC5 complex to promote the MES transition of GSCs through H4 deacetylation.Moreover, cotranscribed miR221 and miR222 can be delivered to macrophages via exosomes to target SOCS3, causing immunosuppressive polarization.Finally, PLX-4720 sensitivity is associated with SPI1 expression and acts on MES GSCs to enhance radiosensitivity.Conclusions: This study demonstrates that targeting SPI1 to block transcription of the MIR222HG cluster helps to reduce radioresistance and combat the immunosuppressive microenvironment in GBM.PLX-4720 is a potential GBM drug and radiosensitizer.
The metallic compound promotes primordial follicle activation and ameliorates fertility deficits in aged mice
Authors: Lincheng Han, Yingying Huang, Biao Li, Weiyong Wang, Yan-li Sun, Xiaodan Zhang, Wenbo Zhang, Shuang Liu, Wenjun Zhou, Wei Xia, Meijia Zhang
Journal: Theranostics (2023)

Aged women and premature ovarian insufficiency (POI) patients have residual dormant primordial follicles that are hard to be activated through a physiological process. However, there are no effective and safe drugs to help them.
Recent progress of emitting long-wavelength carbon dots and their merits for visualization tracking, target delivery and theranostics
Authors: Chao Li, Jiamin Huang, Liwen Yuan, Wenqing Xie, Yupeng Ying, Chengzhe Li, Yahang Yu, Yuanhu Pan, Wei Qu, Haihong Hao, Samah Attia Algharib, Dongmei Chen, Shuyu Xie
Journal: Theranostics (2023)

As a novel strategy for in vivo visualization tracking and monitoring, carbon dots (CDs) emitting long wavelengths (LW, 600-950 nm) have received tremendous attention due to their deep tissue penetration, low photon scattering, satisfactory contrast resolution and high signal-to-background ratios.Although, the mechanism of CDs emitting LW remains controversial and what properties are best for in vivo visualization have not been specifically elucidated, it is more conducive to the in vivo application of LW-CDs through rational design and ingenious synthesis based on the appreciation of the luminescence mechanism.Therefore, this review analyzes the current tracer technologies applied in vivo and their advantages and disadvantages, with emphasis on the physical mechanism of emitting LW fluorescence for in vivo imaging.Subsequently, the general properties and merits of LW-CDs for tracking and imaging are summarized.More importantly, the factors affecting the synthesis of LW-CDs and its luminescence mechanism are highlighted.Simultaneously, the application of LW-CDs for disease diagnosis, integration of diagnosis and therapy are summarized.Finally, the bottlenecks and possible future directions of LW-CDs in visualization tracking and imaging in vivo are detailly discussed.
Photoacoustic imaging for investigating tumor hypoxia: a strategic assessment
Authors: Deyana Nasri, Rayyan Manwar, Ajeet Kaushik, Ekrem Emrah Er, Kamran Avanaki
Journal: Theranostics (2023)

Hypoxia causes the expression of signaling molecules which regulate cell division, lead to angiogenesis, and further, in the tumor microenvironment, promote resistance to chemotherapy and radiotherapy, and induce metastasis. Photoacoustic imaging (PAI) takes advantage of unique absorption characteristics of chromophores in tissues and provides the opportunity to construct images with a high degree of spatial and temporal resolution. In this review, we discuss the physiologic characteristics of tumor hypoxia, and current applications of PAI using endogenous (label free imaging) and exogenous (organic and inorganic) contrast agents. Features of various methods in terms of their efficacy for determining physiologic and proteomic phenomena are analyzed. This review demonstrates that PAI has the potential to understand tumor growth and metastasis development through measurement of regulatory molecule concentrations, oxygen gradients, and vascular distribution.
Functionalization of SF/HAP Scaffold with GO-PEI-miRNA inhibitor Complexes to Enhance Bone Regeneration through Activating Transcription Factor 4: Erratum
Authors: Lingling Ou, Yong Lan, Zhiqiang Feng, Longbao Feng, Junjie Yang, Yu Liu, Liming Bian, Jiali Tan, Renfa Lai, Rui Guo
Journal: Theranostics (2023)

[This corrects the article DOI: 10.7150/thno.34676.].
Engineering polyphenol-based carriers for nucleic acid delivery
Authors: Mingju Shui, Zhejie Chen, Yi Chen, Qin Yuan, Hongyi Li, Chi Teng Vong, Mohamed A. Farag, Shengpeng Wang
Journal: Theranostics (2023)

Gene therapy, an effective medical intervention strategy, is increasingly employed in basic research and clinical practice for promising and unique therapeutic effects for diseases treatment, such as cardiovascular disorders, cancer, neurological pathologies, infectious diseases, and wound healing.However, naked DNA/RNA is readily hydrolyzed by nucleic acid degrading enzymes in the extracellular environment and degraded by lysosomes during intracellular physiological conditions, thus gene transfer must cross complex cellular and tissue barriers to deliver genetic materials into targeted cells and drive efficient activation or inhibition of the proteins.At present, the lack of safe, highly efficient, and non-immunogenic drug carriers is the main drawback of gene therapy.Considering the dense hydroxyl groups on the benzene rings in natural polyphenols that exert a strong affinity to various nucleic acids via hydrogen bonding and hydrophobic interactions, polyphenol-based carriers are promising anchors for gene delivery in which polyphenols serve as the primary building blocks.In this review, the recent progress in polyphenol-assisted gene delivery was summarized, which provided an easily accessible reference for the design of future polyphenol-based gene delivery vectors.Nucleic acids discussed in this review include DNA, short interfering RNAs (siRNA), microRNA (miRNA), double-strand RNA (dsRNA), and messenger RNA (mRNA).
Vertical sleeve gastrectomy-derived gut metabolite licoricidin activates beige fat thermogenesis to combat obesity
Authors: Zhangliu Jin, Wen Meng, Ting Xiao, Jiangming Deng, Jing Wang, Jie Wen, Kai Chen, Liwen Wang, Juanhong Liu, Qingxin Li, Jieyu He, Zheng Wang, Wei Liu, Feng Liu
Journal: Theranostics (2023)

Obesity is a chronic metabolic disease, affecting individuals throughout the world. Bariatric surgery such as vertical sleeve gastrectomy (VSG) provides sustained weight loss and improves glucose homeostasis in obese mice and humans. However, the precise underlying mechanisms remain elusive. In this study, we investigated the potential roles and the mechanisms of action of gut metabolites in VSG-induced anti-obesity effect and metabolic improvement. Methods: High-fat diet (HFD)-fed C57BL/6J mice were subjected to VSG. Energy dissipation in mice was monitored using metabolic cage experiments. The effects of VSG on gut microbiota and metabolites were determined by 16S rRNA sequencing and metabolomics, respectively. The metabolic beneficial effects of the identified gut metabolites were examined in mice by both oral administration and fat pad injection of the metabolites. Results: VSG in mice greatly increased thermogenic gene expression in beige fat, which was correlated with increased energy expenditure. VSG reshaped gut microbiota composition, resulting in elevated levels of gut metabolites including licoricidin. Licoricidin treatment promoted thermogenic gene expression in beige fat by activating the Adrb3-cAMP-PKA signaling pathway, leading to reduced body weight gain in HFD-fed mice. Conclusions: We identify licoricidin, which mediates the crosstalk between gut and adipose tissue in mice, as a VSG-provoked anti-obesity metabolite. Identification of anti-obesity small molecules should provide new insights into treatment options for obesity and its associated metabolic diseases.
Mitochondrial supercomplex assembly regulates metabolic features and glutamine dependency in mammalian cells
Authors: Kun Zhang, Linjie Chen, Bo Wang, Deyu Chen, Xianglai Ye, Xinyu Han, Quan Fang, Can Yu, Jia Wu, Sihan Guo, Lifang Chen, Yu Shi, Lan Wang, Huang Cheng, Hao Li, Lu Shen, Qiongya Zhao, Liqin Jin, Jianxin Lyu, Hezhi Fang
Journal: Theranostics (2023)

Rationale: Mitochondria generate ATP via the oxidative phosphorylation system, which mainly comprises five respiratory complexes found in the inner mitochondrial membrane.A high-order assembly of respiratory complexes is called a supercomplex.COX7A2L is a supercomplex assembly factor that has been well-investigated for studying supercomplex function and assembly.To date, the effects of mitochondrial supercomplexes on cell metabolism have not been elucidated.Methods: We depleted COX7A2L or Cox7a2l in human and mouse cells to generate cell models lacking mitochondrial supercomplexes as well as in DBA/2J mice as animal models.We tested the effect of impaired supercomplex assembly on cell proliferation with different nutrient supply.We profiled the metabolic features in COX7A2L -/-cells and Cox7a2l -/-mice via the combined use of targeted and untargeted metabolic profiling and metabolic flux analysis.We further tested the role of mitochondrial supercomplexes in pancreatic ductal adenocarcinoma (PDAC) through PDAC cell lines and a nude mouse model.Results: Impairing mitochondrial supercomplex assembly by depleting COX7A2L in human cells reprogrammed metabolic pathways toward anabolism and increased glutamine metabolism, cell proliferation and antioxidative defense.Similarly, knockout of Cox7a2l in DBA/2J mice promoted the use of proteins/amino acids as oxidative carbon sources.Mechanistically, impaired supercomplex assembly increased electron flux from CII to CIII/CIV and promoted CII-dependent respiration in COX7A2L -/-cells which further upregulated glutaminolysis and glutamine oxidation to accelerate the reactions of the tricarboxylic acid cycle.Moreover, the proliferation of PDAC cells lacking COX7A2L was inhibited by glutamine deprivation.Conclusion: Our results reveal the regulatory role of mitochondrial supercomplexes in glutaminolysis which may fine-tune the fate of cells with different nutrient availability.
DNA-PKcs inhibitors sensitize neuroendocrine tumor cells to peptide receptor radionuclide therapy <i>in vitro</i> and <i>in vivo</i>
Authors: Thom G.A. Reuvers, Nicole S. Verkaik, Debra Stuurman, Corrina de Ridder, Marian C. Clahsen-van Groningen, Erik de Blois, Julie Nonnekens
Journal: Theranostics (2023)

Peptide receptor radionuclide therapy (PRRT) increases progression-free survival and quality of life of neuroendocrine tumor (NET) patients, however complete cures are rare and dose-limiting toxicity has been reported. PRRT induces DNA damage of which DNA double strand breaks (DSBs) are the most cytotoxic. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a key player in DSB repair and its inhibition therefore is a potential way to enhance PRRT efficacy without increasing the dosage.
Generation of host-directed and virus-specific antivirals using targeted protein degradation promoted by small molecules and viral RNA mimics
Authors: Nan Zhao, Jessica Sook Yuin Ho, Fanye Meng, Simin Zheng, Andrew P. Kurland, Lu Tian, Martha Rea-Moreno, Xiangyang Song, Ji-Seon Seo, H. Ümit Kaniskan, Aartjan J.W. te Velthuis, Domenico Tortorella, Ya-Wen Chen, Jeffrey R. Johnson, Jian Jin, Ivan Marazzi
Journal: Cell Host & Microbe (2023)

Targeted protein degradation (TPD), as exemplified by proteolysis-targeting chimera (PROTAC), is an emerging drug discovery platform. PROTAC molecules, which typically contain a target protein ligand linked to an E3 ligase ligand, recruit a target protein to the E3 ligase to induce its ubiquitination and degradation. Here, we applied PROTAC approaches to develop broad-spectrum antivirals targeting key host factors for many viruses and virus-specific antivirals targeting unique viral proteins. For host-directed antivirals, we identified a small-molecule degrader, FM-74-103, that elicits selective degradation of human GSPT1, a translation termination factor. FM-74-103-mediated GSPT1 degradation inhibits both RNA and DNA viruses. Among virus-specific antivirals, we developed viral RNA oligonucleotide-based bifunctional molecules (Destroyers). As a proof of principle, RNA mimics of viral promoter sequences were used as heterobifunctional molecules to recruit and target influenza viral polymerase for degradation. This work highlights the broad utility of TPD to rationally design and develop next-generation antivirals.
Clinical quantitative coronary artery stenosis and coronary atherosclerosis imaging: a Consensus Statement from the Quantitative Cardiovascular Imaging Study Group
Authors: Aldo J. Vázquez Mézquita, Federico Biavati, Volkmar Falk, Hatem Alkadhi, Reza Hajhosseiny, Pál Maurovich-Horvat, Robert Manka, Sebastian Kozerke, Matthias Stuber, Thorsten Derlin, Keith M. Channon, Ivana Išgum, Adriaan Coenen, Bernhard Foellmer, Damini Dey, Rick H. J. A. Volleberg, Felix G. Meinel, Marc R. Dweck, Jan J. Piek, Tim van de Hoef, Ulf Landmesser, Giulio Guagliumi, Andreas A. Giannopoulos, René M. Botnar, Ramzi Khamis, Michelle C. Williams, David E. Newby, Marc Dewey
Journal: Nature Reviews Cardiology (2023)
Editorial Board
Authors: Zuhair Ballas, Iowa City, Iowa Deputy, David Huston, Rachel Miller, New York, Andrea Apter, Leonard Philadelphia, Nashville Bacharier, Claus Bachert, Joshua Boyce, Javier Chinen, Raif Geha, Johann Gudjonsson, Ann Arbor, Mich Kenji Kabashima, Corinne Keet, Chapel Hill, Carole Ober, Wanda Phipatanakul, Harald Renz, Marburg Germany, Marc Rothenberg, Cincinnati Ohio, Hirohisa Saito, Stefan Vieths, Langen Germany, Stephan Weidinger
Journal: Journal of Allergy and Clinical Immunology (2023)
Robot-assisted Radical Prostatectomy with the Dexter Robotic System: Initial Experience and Insights into On-demand Robotics
Authors: Damien Thillou, Humphrey Robin, Coline Ricolleau, Nadia Ali Benali, Aurélien Forgues, Damien Emeriau, Hubert Mignot, Guillaume Hugues
Journal: European Urology (2023)
Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell carcinoma after progression with previous immune checkpoint inhibitor treatment (CONTACT-03): a multicentre, randomised, open-label, phase 3 trial
Authors: Sumanta Kumar Pal, Laurence Albiges, Piotr Tomczak, Cristina Suárez, Martin H Voss, Guillermo de Velasco, Jad Chahoud, Anastasia Mochalova, Giuseppe Procopio, Hakim Mahammedi, Friedemann Zengerling, Chan Kim, Takahiro Osawa, Martín Angel, Suyasha Gupta, Omara Khan, Guillaume Bergthold, Bo Liu, Melania Kalaitzidou, Mahrukh Huseni, Christian Scheffold, Thomas Powles, Toni K Choueiri
Journal: The Lancet (2023)
Portable, wearable and implantable artificial kidney systems: needs, opportunities and challenges
Authors: David Loureiro Ramada, Joost de Vries, Jeroen Vollenbroek, Nazia Noor, Odyl ter Beek, Silvia M. Mihăilă, Fokko Wieringa, Rosalinde Masereeuw, Karin Gerritsen, Dimitrios Stamatialis
Journal: Nature Reviews Nephrology (2023)

Haemodialysis is life sustaining but expensive, provides limited removal of uraemic solutes, is associated with poor patient quality of life and has a large carbon footprint. Innovative dialysis technologies such as portable, wearable and implantable artificial kidney systems are being developed with the aim of addressing these issues and improving patient care. An important challenge for these technologies is the need for continuous regeneration of a small volume of dialysate. Dialysate recycling systems based on sorbents have great potential for such regeneration. Novel dialysis membranes composed of polymeric or inorganic materials are being developed to improve the removal of a broad range of uraemic toxins, with low levels of membrane fouling compared with currently available synthetic membranes. To achieve more complete therapy and provide important biological functions, these novel membranes could be combined with bioartificial kidneys, which consist of artificial membranes combined with kidney cells. Implementation of these systems will require robust cell sourcing; cell culture facilities annexed to dialysis centres; large-scale, low-cost production; and quality control measures. These challenges are not trivial, and global initiatives involving all relevant stakeholders, including academics, industrialists, medical professionals and patients with kidney disease, are required to achieve important technological breakthroughs. Portable, wearable and implantable artificial kidney systems require compact and efficient dialysate regeneration systems and novel membranes for improved toxin removal and long-term patency. Here, the authors discuss efforts to overcome these challenges and future perspectives for achieving miniaturized dialysis.
The parabrachial nucleus elicits a vigorous corticosterone feedback response to the pro-inflammatory cytokine IL-1β
Authors: Ferdinand Jagot, Romane Gaston-Breton, Ana Jeemin Choi, Maud Pascal, Lena Bourhy, Romane Dorado-Doncel, Karl-Klaus Conzelmann, Pierre-Marie Lledo, Gabriel Lepousez, Gérard Eberl
Journal: Neuron (2023)
Quantification of intratumoural heterogeneity in mice and patients via machine-learning models trained on PET–MRI data
Authors: Prateek Katiyar, Johannes Schwenck, Leonie Frauenfeld, Mathew R. Divine, Vaibhav Agrawal, Ursula Kohlhofer, Sergios Gatidis, Roland Kontermann, Alfred Königsrainer, Leticia Quintanilla-Martinez, Christian la Fougère, Bernhard Schölkopf, Bernd J. Pichler, Jonathan A. Disselhorst
Journal: Nature Biomedical Engineering (2023)
CaMK1D signalling in AgRP neurons promotes ghrelin-mediated food intake
Authors: Karl Vivot, Gergö Meszaros, Evanthia Pangou, Zhirong Zhang, Mengdi Qu, Eric Erbs, Gagik Yeghiazaryan, Mar Quiñones, Erwan Grandgirard, Anna Schneider, Etienne Clauss–Creusot, Alexandre Charlet, Maya Faour, Claire Martin, Fedor Berditchevski, Izabela Sumara, Serge Luquet, Peter Kloppenburg, Ruben Nogueiras, Romeo Ricci
Journal: Nature Metabolism (2023)
Scribble mis-localization induces adaptive resistance to KRAS G12C inhibitors through feedback activation of MAPK signaling mediated by YAP-induced MRAS
Authors: Yuta Adachi, Ryo Kimura, Kentaro Hirade, Shogo Yanase, Yuki Nishioka, Natsumi Kasuga, Rui Yamaguchi, Hiromichi Ebi
Journal: Nature Cancer (2023)
A Treg-specific long noncoding RNA maintains immune-metabolic homeostasis in aging liver
Authors: Chenbo Ding, Zhibin Yu, Esen Sefik, Jing Zhou, Eleanna Kaffe, Gaoyang Wang, Bin Li, Richard A. Flavell, Weiguo Hu, Youqiong Ye, Hua-Bing Li
Journal: Nature Aging (2023)